Back to search results

Varenicline and Accelerated TMS for Quitting Nicotine Use

This study is looking at whether a combination of varenicline (an FDA-approved medication) and accelerated Transcranial Magnetic Stimulation (aTMS), which uses magnetic pulses to stimulate brain cells, can help adults quit smoking or vaping nicotine. Researchers want to see if receiving active aTMS plus varenicline leads to higher rates of quitting nicotine and lower cravings, compared to a placebo (inactive) aTMS with varenicline. You could be eligible if you are 18-65 years old, speak English, want to quit nicotine in the next month, and have nicotine dependence. The study will measure if you can stay nicotine-free for weeks 9-12 of the study.

Study design
This is a randomized, double-blind study with 30 participants. You will be assigned to one of two groups: active aTMS or sham (inactive) aTMS, both combined with varenicline.
What's involved
You will complete two brain MRI scans, take varenicline daily for 12 weeks, and complete one day of up to 20 TMS treatments. You will also receive 12 sessions of nicotine cessation counseling and take a single dose of D-cycloserine or a placebo pill.
Compensation
Not stated in the trial record.
Follow-up
The study measures your nicotine abstinence between weeks 9 and 12, and brain activity at baseline and week 12.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT07145866

Varenicline and Accelerated Transcranial Magnetic Stimulation (TMS) for Quitting Nicotine Use (Pilot Study)

Recruiting
PHASE4Ages 18–65InterventionalTreatment
Massachusetts General Hospital
~30 participants
Updated 2026-07-13 on ClinicalTrials.gov
What's tested:VareniclineTranscranial Magnetic StimulationTranscranial Magnetic Stimulation ShamNicotine Cessation CounselingD-cycloserine

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Biochemically-confirmed continuous nicotine abstinence across study weeks 9-12
Measured over Week 9-Week 12
+2 more outcomes measured

Conditions

Nicotine Dependence
Transcranial Magnetic Stimulation
Vaping
Smoking Cessation
Smoking (Tobacco) Addiction

Explore related trials

Nicotine DependenceSmoking Cessation

Where it's being run

1 sites across 1 states
Massachusetts1

Study leadership

  • Jodi M Gilman, PhD · PRINCIPAL_INVESTIGATOR · Massachusetts General Hospital

Who to contact

Jodi M Gilman, PhD
[email protected]
617-643-7293
Email the study team

Opens a ready-to-send draft in your own email app — review before sending.

Do you actually qualify for this trial?

Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.

Check eligibility for this trial ~2 min · HIPAA-protected · delete anytime
Eligibility criteria

Inclusion

Age ≥ 18 and ≤65;
The ability to give written, informed consent;
Fluency in English;
Reported interest in quitting nicotine vaping or smoking within the next month;
Nicotine dependence, as defined by a score of ≥4 on the 10-question E-cigarette Dependence Inventory (ECDI) or Fagerström Test for Nicotine Dependence (FTND);
Smoke or vape nicotine daily for at least the past 90 days, as confirmed by self-report and timeline follow-back methods;
Saliva cotinine \>30ng/mL;

Exclusion

Pregnancy or breastfeeding;
Use of smoking cessation pharmacotherapy in the past month;
Unwilling to abstain during the study from using smoking cessation aids other than those provided by the study;
Prior adverse drug reaction to varenicline;
Contraindication to D-Cycloserine (including allergy to D-Cycloserine, significant renal impairment or known kidney disease, pregnancy)
Receiving or planning to receive other TMS treatments or investigational drugs during course of participation
Contraindications to TMS (including seizures, metallic implants, severe existing tinnitus, etc.);
Contraindications to MRI (including presence of a cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia);
Inpatient psychiatric hospitalization or suicide attempts in the past six months, or recent active suicidal ideation or suicidal behavior identified at enrollment or baseline visits;
History of seizures and/or history of TBI subtypes associated with elevated seizure risk (e.g. penetrating injury and intraparenchymal hemorrhage)
History of unstable neurological illness or major medical illness, such as epilepsy or renal impairment, in the past six months, unless clearly resolved;
In the opinion of the investigators, evidence of active problem substance use severe enough to compromise ability to safely participate;
In the opinion of the investigators, unable to safely participate in this study and/or provide reliable data (e.g., claustrophobia, unable to tolerate TMS or MRI procedures, etc.).

What this trial measures

  • Biochemically-confirmed continuous nicotine abstinence across study weeks 9-12Week 9-Week 12

    Point-prevalence abstinence from e-cigarette use was defined as self-report of no e-cigarette use since the last visit, bioverified by saliva cotinine \<30 ng/ml. Continuous abstinence is defined as observed point-prevalence abstinence over specified study visits at weeks 9, 10, 11 and 12. The primary analysis will compare the proportion of participants achieving continuous abstinence in the enhanced aTMS + varenicline group versus the Sham + varenicline group using a chi-square test. If expected cell counts are low (\<5 in any cell), Fisher's exact test will be used instead.

  • Resting State Functional Connectivity (rsFC)Baseline, Week 12

    Within-network resting state Functional Connectivity (rsFC) will be computed by extracting the mean BOLD time series from each region of interest comprising the addiction circuit and calculating pairwise Pearson correlations, which will then be Fisher z-transformed and averaged across all ROI pairs to derive a single within-network rsFC metric per participant at each time point. To isolate effects at the circuit level rather than changes induced by stimulation of the medial prefrontal cortex (mPFC) target site itself, the mPFC stimulation region will be excluded from the connectivity analyses. The primary analytic approach will use a linear mixed-effects model with fixed effects for time (baseline vs. post-treatment), treatment group (TMS vs. sham TMS), and their interaction, as well as a random intercept for each participant.

  • Change in Insula Activation to Nicotine Cues During a Cue Reactivity Task Measured by fMRIBaseline, Week 12

    Neural responses to nicotine and neutral cues will be modeled, convolved with the canonical hemodynamic response function, and contrast images for nicotine \> neutral cues will be generated for each participant at each time point. These contrast images will be entered into second-level analyses to test group-level effects. The primary region of interest (ROI) will be the bilateral anterior insula, defined using an anatomical mask from the Harvard-Oxford atlas. The main analytic model will be a mixed-effects repeated-measures ANOVA or linear mixed-effects model with fixed effects of time (pre vs. post), treatment group (TMS + varenicline vs. sham TMS + varenicline), and their interaction, with subject-level random intercepts. The key test of our hypothesis is the time × treatment interaction within the anterior insula ROI, which reflects whether treatment modulates cue-elicited insula activity.